Morphological Changes of Gingiva in Streptozotocin Diabetic Rats

Gingivitis and periodontitis are chronic bacterial diseases of the underlying and surrounding tooth tissues. Diabetes mellitus is responsible for tooth deprivation both by decay and periodontal disease. The streptozotocin-induced diabetes results in a diabetic status in experimental animals similar to that observed in diabetes patients. The aim of the study was to investigate the relationship between the gingival lesions and the microangiopathy changes in streptozotocin-induced diabetes mellitus. Forty male Wistar rats were divided into two groups (control and experimental). Diabetes mellitus was induced by 45 mg/kg IV streptozotocin. The histological investigation of the marginal gingival and the relevant gingival papilla showed inflammation of the lamina propria and the squamous epithelium as well as marked thickness of the arteriole in the diabetic group, but no changes were observed in the control group. The results suggested a probable application of a routine gingival histological investigation in diabetic patients in order to control the progress of disease complications. It may be concluded that histological gingival investigation can be used as a routine assay for the control of the diabetic disease and prevention of its complications

EFFECT OF FORCEPS SIZE AND MODE OF ORIENTATION ON ENDOSCOPIC SMALL-BOWEL BIOPSY EVALUATION

Endoscopy is increasingly being used to obtain duodenal biopsy specimens in suspected small intestinal malabsorption. We have prospectively evaluated the effect of standard and jumbo biopsy forceps, as well as the mode of orientation of the specimens (naked eye or stereomicroscopy), on duodenal biopsy weight, length, depth, and orientation in 18 consecutive patients. A pair of biopsy specimens was obtained from each patient by each type of forceps in random order. After they had been weighed, one biopsy specimen from each pair was oriented stereomicroscopically and all four were blindly evaluated by two pathologists. The biopsy specimens obtained with the jumbo forceps were significantly larger (15.9 +/- 6.9 mg, mean +/- SD) and longer (0.6 + 0.2 cm) than those obtained with the standard forceps (8.0 +/- 1.3 mg, 0.4 +/- 0.2 cm, respectively; p < 0.001). Seventy-two percent of the jumbo biopsy specimens that were oriented with stereomicroscopy included a minimum of four villi in a row, as compared to 44% of the eye-oriented jumbo specimens and less than 39% of the standard specimens, irrespective of the mode of orientation (p = 0.02). These results indicate that the jumbo forceps is superior to the standard, because it produces a larger duodenal mucosal specimen, usually suitable for optimal histologic evaluation when oriented with stereomicroscopy

Nifedipine-induced histological changes in the parotid glands of hypertensive rats

Nifedipine is a widely used anti-anginal and anti-hypertensiveagent. It is associated with significant gingival changes attributedmore to collagen hyperplasia than to enhancement of proteinsynthesis. We investigated the influence of nifedipine on morphologicalchanges in the parotid glands of rats in a model of hypertension.Twenty-eight male Wistar rats (8-10 weeks; 200 ± 15 g) were dividedinto four groups (A-D). Hypertension was induced by surgical meansin groups C and D. Animals in groups B and D were treated with nifedipine(0.85 mg/kg) via a gastroesophageal catheter the day after surgery(experimental day-1) for 2 weeks. A significant difference was observedbetween the control group and nifedipine group and betweenthe control group and hypertension group with regard to the weightof the parotid gland and its surface area. Histological findings demonstratedchanges in the parotid glands of hypertensive animals withmild vessel dilatation and infiltration of inflammatory cells. These histologicalfindings seemed to be due more to changes in venous functionthan to alterations in gland architecture

H3 propranolol serum levels following lidocaine administration in rats with CCL4 - induced liver damage

Liver disease alters the pharmacokinetic and pharmacodynamic properties of hepatically eliminated drugs. The main factors influenced are plasma albumin levels, enzyme balance (induction & inhibition) and drug binding to tissue proteins. The influence of lidocaine on serum, heart and liver propranolol levels in Wistar rats after liver injury induced by carbon tetrachloride CCl4 0.4 ml/kg × 2/wkl, was investigated. 40 male Wistar rats were divided into four groups (I, II, III, IV; n=10), Group I animals received only propranolol (labelled + cold substance) 40 mg/kg/12 h p.o., group II propranolol plus lidocaine in a single dose of 4mg/kg s.c., group III was treated with CCl4 for 6 weeks and received propranolol ×2 at the same dosage as group I, while group VI was treated with CCl4 and the same drug dosage as group II. The simultaneous administration of H 3-propranolol and lidocaine increased propranolol levels in the serum and tissues. The liver in damaged animals showed an increase of propranolol level under lidocaine co-administration, probably due to CCl4 - induced liver enzyme activity, resulting in a rapid propranolol metabolism or to competition between both drug protein binding sites. The increased propranolol levels in the heart after lidocaine administration were probably due to attributed to its high affinity for heart tissue. Consequently, as regards the therapeutic approach for patients with liver disease receiving propranolol their propranolol dosage should be reduced when lidocaine is co-administered

Comparative Cancer Cell Signaling in Muscle-Invasive Urothelial Carcinoma of the Bladder in Dogs and Humans.

Muscle-invasive urothelial carcinoma (MIUC) is the most common type of bladder malignancy in humans, but also in dogs that represent a naturally occurring model for this disease. Dogs are immunocompetent animals that share risk factors, pathophysiological features, clinical signs and response to chemotherapeutics with human cancer patients. This review summarizes the fundamental pathways for canine MIUC initiation, progression, and metastasis, emerging therapeutic targets and mechanisms of drug resistance, and proposes new opportunities for potential prognostic and diagnostic biomarkers and therapeutics. Identifying similarities and differences between cancer signaling in dogs and humans is of utmost importance for the efficient translation of in vitro research to successful clinical trials for both species

Comparative Cancer Cell Signaling in Muscle-Invasive Urothelial Carcinoma of the Bladder in Dogs and Humans

Muscle-invasive urothelial carcinoma (MIUC) is the most common type of bladder malignancy in humans, but also in dogs that represent a naturally occurring model for this disease. Dogs are immunocompetent animals that share risk factors, pathophysiological features, clinical signs and response to chemotherapeutics with human cancer patients. This review summarizes the fundamental pathways for canine MIUC initiation, progression, and metastasis, emerging therapeutic targets and mechanisms of drug resistance, and proposes new opportunities for potential prognostic and diagnostic biomarkers and therapeutics. Identifying similarities and differences between cancer signaling in dogs and humans is of utmost importance for the efficient translation of in vitro research to successful clinical trials for both species

The Androgen Receptor in Prostate Cancer: Effect of Structure, Ligands and Spliced Variants on Therapy.

The androgen receptor (AR) plays a predominant role in prostate cancer (PCa) pathology. It consists of an N-terminal domain (NTD), a DNA-binding domain (DBD), a hinge region (HR), and a ligand-binding domain (LBD) that binds androgens, including testosterone (T) and dihydrotestosterone (DHT). Ligand binding at the LBD promotes AR dimerization and translocation to the nucleus where the DBD binds target DNA. In PCa, AR signaling is perturbed by excessive androgen synthesis, AR amplification, mutation, or the formation of AR alternatively spliced variants (AR-V) that lack the LBD. Current therapies for advanced PCa include androgen synthesis inhibitors that suppress T and/or DHT synthesis, and AR inhibitors that prevent ligand binding at the LBD. However, AR mutations and AR-Vs render LBD-specific therapeutics ineffective. The DBD and NTD are novel targets for inhibition as both perform necessary roles in AR transcriptional activity and are less susceptible to AR alternative splicing compared to the LBD. DBD and NTD inhibition can potentially extend patient survival, improve quality of life, and overcome predominant mechanisms of resistance to current therapies. This review discusses various small molecule and other inhibitors developed against the DBD and NTD-and the current state of the available compounds in clinical development

Histopathological evaluation and redox assessment in blood and kidney tissues in a rabbit contrast-induced nephrotoxicity model

Contrast-induced nephropathy (CIN) is a leading cause of hospital-acquired acute kidney injury as a result of iodinated contrast-media use for diagnostic purposes. Pathophysiology remains unclear. In the present study iopromide was administered to New Zealand white rabbits without any prior intervention. Oxidative stress was assessed in blood and tissue level at three anatomical kidney areas (medullary, cortical, juxtamedullary). Histopathological evaluation was also performed. Serum creatinine and urea increased in the CIN groups over 25% at two hours after administration and returned to baseline at 48 h. In kidney tissues, a significant reduction (40%) of catalase in renal cortexes of the CIN groups was observed. Necrosis and tubular vacuolization was also noted that correlated with urea and creatinine levels. Lipid peroxidation decreased at 10 h after administration (>45%) and remained low even at 48 h. Plasma protein carbonyls were significantly increased (67%) in 2 h and dropped later. Serum levels of creatinine and urea at 24 and 48 h significantly correlated with the Total Antioxidant Activity and lipid peroxidation, respectively. Oxidative stress is shown to be involved in CIN development in the rabbit, with more pronounced effects to be confined to the cortex and outer stripe of the outer medulla. © 201

The Androgen Receptor in Prostate Cancer: Effect of Structure, Ligands and Spliced Variants on Therapy.

The androgen receptor (AR) plays a predominant role in prostate cancer (PCa) pathology. It consists of an N-terminal domain (NTD), a DNA-binding domain (DBD), a hinge region (HR), and a ligand-binding domain (LBD) that binds androgens, including testosterone (T) and dihydrotestosterone (DHT). Ligand binding at the LBD promotes AR dimerization and translocation to the nucleus where the DBD binds target DNA. In PCa, AR signaling is perturbed by excessive androgen synthesis, AR amplification, mutation, or the formation of AR alternatively spliced variants (AR-V) that lack the LBD. Current therapies for advanced PCa include androgen synthesis inhibitors that suppress T and/or DHT synthesis, and AR inhibitors that prevent ligand binding at the LBD. However, AR mutations and AR-Vs render LBD-specific therapeutics ineffective. The DBD and NTD are novel targets for inhibition as both perform necessary roles in AR transcriptional activity and are less susceptible to AR alternative splicing compared to the LBD. DBD and NTD inhibition can potentially extend patient survival, improve quality of life, and overcome predominant mechanisms of resistance to current therapies. This review discusses various small molecule and other inhibitors developed against the DBD and NTD-and the current state of the available compounds in clinical development